tbuckley/cabot-search huggingface dataset:
Efficacy and safety of XELOX combined with anlotinib and penpulimab vs XELOX as adjuvant therapy in ctDNA-positive gastric and esophagogastric junction adenocarcinoma: A protocol for a randomized, controlled, multicenter phase II clinical trial—EXPLORING study.
Authors: Yizhang Chen, Jie Tang, Fen Guo, Wei Li, Jiaguang Zhang, Xinyi Zhang, Yitong Tian, Lanlan Pan, Ling Ma, Yongqian Shu, Xiaofeng Chen
Journal: Journal of Clinical Oncology (2023)

TPS486 Background: The clinical benefit of current postoperative adjuvant chemotherapy for gastric adenocarcinoma/gastroesophageal junction adenocarcinoma (GA/GEJA) leaves much to be desired. CtDNA could serve as a potential marker to identify patients (pts) who are most at risk of recurrence. Reinforcing standard adjuvant chemotherapy with immunotherapy has already been indicated to significantly boost clinical benefit, albeit such evidence is rare in GA/GEJA. Here, we intend to prove the clinical benefit of the reinforcement of adjuvant chemotherapy with immunotherapy in patients who are deemed high risk of recurrence by ctDNA analysis, in hope of shedding light on further improvements in adjuvant therapy for GA/GEJA. Methods: This study is designed as a prospective, randomized, controlled, multicenter phase II study in patients histologically or cytologically diagnosed with CG/GEJC (Siewert III), 18-75 years, ECOG PS 0-1, underwent D2 gastrectomy and achieved R0 or R1 resection. Beginning from February 2022, a total of 270 stage III patients will be enrolled and subjected to ctDNA sequencing, and those with positive results will subsequently be randomized 1:1 to arm A or B. CtDNA-negative patients will be assigned to arm C and pts who had ctDNA positive but failed to be randomized will be assigned to arm D. Pts in arm A will receive anlotinib, penpulimab and XELOX for 6-8 cycles, maintained with anlotinib and penpulimab for up to 1 year, while pts in arm B will receive XELOX alone for 6-8 cycles. Pts in arms C&amp;D will receive the investigator’s choice of therapy. Arms A&amp;B will be monitored for ctDNA levels on a 3-month cycle for 1 year. Survival data, laboratory findings, imaging reports and nutritional status will be regularly followed-up in all arms. The primary endpoint is the median disease-free survival (DFS) of arm A versus arm B determined via CT/MRI imaging. Secondary endpoints include the median DFS of arm B versus arm C, the 2- and 3-year DFS rates, overall survival (OS), the impact of hallmark molecules (presumably ctDNA) on the treatment response, adverse events (AEs), and the impact of nutrition status and exercise on recurrence. Clinical trial information: NCT05494060 .
Phase II study of the combination of durvalumab, tremelimumab, and paclitaxel as second-line chemotherapy in biomarker-selected patients with metastatic gastric cancer.
Authors: Keun-Wook Lee, Hark Kyun Kim, Min-Hee Ryu, Dae Young Zang, Ji-Won Kim, Bum Jun Kim, Hyung-Don Kim, Jin Won Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2023)

401 Background: Currently, ramucirumab plus paclitaxel is the standard second-line chemotherapy in metastatic gastric cancer (mGC), however, its efficacy is very limited. MSI, PD-L1 (CD274), and EBV have been suggested as predictive biomarkers for immune checkpoint inhibitors in mGC. This study was conducted to evaluate efficacy and safety of the combination of durvalumab, tremelimumab, and paclitaxel as a second-line chemotherapy in mGC with potential biomarkers for immune checkpoint inhibitors. Methods: The combination of durvalumab, tremelimumab, and paclitaxel consisted of 1500 mg of i.v. durvalumab on day 1, every 4 weeks for 13 cycles, 75 mg of i.v. tremelimumab on day 1 every 4 weeks for 4 cycles, and 60 mg/m 2 of i.v. paclitaxel on days 1, 8, and 15, every 4 weeks until disease progression or unacceptable toxicities. Patients (pts) with MSI-high mGC, EBV-positive mGC, or mGC with CD274 amplification, mutations of mismatch repair or POL gene, or tumor mutation burden (TMB) &gt;5/Mb were included in second-line setting. Results: Forty-eight pts were enrolled. Overall response rate (ORR) was 52.1% with complete response in 4 (8.3%) pts, partial response in 21 (43.8%), stable disease in 14 (29.2%), and progressive disease in 8 (16.7%), and with response not evaluable in 1 (2.0%). With a median follow-up of 18.0 months (range, 7.1-39.4), the median progression-free survival (PFS) and overall survival (OS) were 5.3 months (95% CI, 3.7-6.9) and 13.1 months (95% CI, 5.2-21.0 ), respectively. Compared to mGC with other genetic alterations (n=25), mGC with TMB &gt;20/Mb or MSI-high mGC (n=23) tended to have a higher ORR (56.5% vs 48%), and a prolonged PFS (median 7.2 vs 4.5 months; 44.0 vs 20.8% at 1 year). The combination chemotherapy was generally well tolerable; treatment-related grade 3 or 4 adverse events with frequency &gt;5% included only neutropenia (10.4%) and anemia (8.3%), and there was no treatment-related death. Conclusions: The combination chemotherapy of durvalumab, tremelimumab, and paclitaxel showed encouraging efficacy, especially in mGC with TMB &gt;20/Mb or MSI-high mGC, as a second-line chemotherapy with manageable toxicities in biomarker-selected mGC. Clinical trial information: NCT03751761 .
Neoadjuvant chemoradiation does not improve outcomes for patients undergoing resection for upper rectal cancer: A US Rectal Cancer Consortium analysis.
Authors: Caroline Medin, Adriana C. Gamboa, Emilie Warren, Scott E. Regenbogen, Samantha Hendren, Jennifer Holder-Murray, Matthew Kalady, Aslam Ejaz, Alexander Hawkins, Matthew Silviera, Shishir K. Maithel, Glen C. Balch
Journal: Journal of Clinical Oncology (2023)

143 Background: The use of neoadjuvant chemoradiation (NCRT) for upper rectal cancer remains controversial. Our aim was to determine whether NCRT was associated with improved outcomes. Methods: The US Rectal Cancer Consortium was queried for patients who underwent resection of non-metastatic upper rectal cancer (≥12cm from anal verge) from 2007-2017. Primary outcomes were recurrence-free (RFS) and overall survival (OS). Secondary outcomes were postoperative complications. Results: 193 pts met inclusion criteria; 100 (52%) did not receive NCRT and 93 (48%) did. Median age was similar between groups (non-NCRT: 62 yrs; NCRT: 57 yrs; p=0.71). Patients in each group had similar gender and pathological stage (non-NCRT: 22% stage I, 32% stage II, 36% stage III; NCRT: 21% stage I, 23% stage II, 33% stage III; p=0.143). Median follow-up was 31 months (non-NCRT) and 34 months (NCRT). On Kaplan-Meier analysis, NCRT was not associated with improved RFS compared to non-NCRT (3-year RFS 85% vs. 80%; p=0.34) or OS (3-year OS 88% vs. 90%; p=0.49). This finding persisted on multivariable cox regression. R0 resection rate was similar between groups at 99% (non-NCRT) and 97% (NCRT; p=0.27). Anastomotic leak occurred in 11% of both cohorts. Creation of a diverting loop ileostomy (DLI) was nearly 3 times higher in NCRT (82%) versus non-NCRT patients (29%; p&lt;0.001). Conclusions: Among patients with non-metastatic upper rectal cancer, NCRT did not improve survival or recurrence rates, but was associated with a nearly threefold higher DLI rate. Although NCRT is a mainstay of treatment for lower rectal cancer, our results do not support its use in upper rectal cancer. [Table: see text]
Updated results of ALTER-C002: Anlotinib combined with CAPEOX as first-line treatment in RAS/BRAF wild-type unresectable metastatic colorectal cancer.
Authors: Ke-Feng Ding, Yue Liu, Qian Xiao, Jinjie He, Hanguang Hu, Jinlin Du, Yuping Zhu, Jiaqi Chen, Zhuo Liu, Jianping Wang, Lifeng Sun, Dong Xu, Jun Li, Xiujun Liao, Jianwei Wang, Yibo Cai, Cheng Cai, Zhekang Jin, Ying Yuan
Journal: Journal of Clinical Oncology (2023)

138 Background: Anlotinib is an oral multi-target tyrosine kinase inhibitor, mainly targeting VEGFR1-3, FGFR 1-4, PDGFR a/b and c-kit. Previous trial had demonstrated that anlotinib monotherapy was effective and safe in advanced colorectal cancer. ALTER-C002 trial is an open-label, single-arm, phase II study, aimed to evaluate the efficacy and safety of anlotinib plus CAPEOX as first-line therapy in patients with RAS/ BRAF wild-type unresectable metastatic colorectal cancer (mCRC). Preliminary results demonstrated significant antitumor activity and manageable toxicity. Here we reported the updated results at the data cutoff of August 19, 2022. Methods: RAS/BRAF wild-type unresectable mCRC patients with no prior systemic treatment received anlotinib (12 mg p.o. qd, d1-d14, q3w), capecitabine (850 mg/m 2 p.o., bid, d1-d14, q3w) and oxaliplatin (130 mg/m 2 i.v., d1, q3w) for 6 cycles followed by anlotinib and capecitabine as maintenance therapy until disease progression. Tumor response was assessed every 6 weeks according to RECIST v1.1 by investigator. The primary endpoint was ORR, and secondary endpoints included safety, DCR, DOR and PFS. Results: From Nov 2019 to February 2021, 30 eligible patients were enrolled, of whom, median age was 60y (range, 32-72y), 26 (86.7%) had left colon or rectal cancer, and 25 (83.3%) had liver metastases. The ORR was 76.7% (95% CI, 57.7-90.1%) with 2 patient achieved a complete response (CR); DCR was 93.3% (95% CI, 77.9-99.2%). At the data cutoff date, the median DOR was 7.9 months (95% CI, 4.3–11.4) and the median DOT was 8.38 months (95%CI, 5.9-10.9). The median OS has not reached yet, the 24-month OS rate was 72.8% (95%CI, 50.7-86.3%) and the 30-month OS rate was 58.3% (95%CI:25.5-80.8%). Grade 3-4 treatment-emergent adverse events (TEAEs) occurred in 25 (83.3%) patients; the most common grade 3 or 4 TEAEs ( &gt; 10%) were hypertension (50%, 15/30 pts), neutropenia (26.7%, 8/30 pts) and diarrhea (13.3%, 4/30 pts). No grade 5 treatment-related events occurred. Conclusions: Anlotinib combined with CAPEOX exhibited promising ORR in the first-line treatment of mCRC compared to those of previous treatment. A longer follow-up is needed for a more complete assessment, and we launched a phase III, multicenter, open-label trial to assess the efficacy of this regimen comprehensively. Clinical trial information: NCT04080843 .
Short-course radiotherapy in rectal cancer: A single-center experience in Argentina.
Authors: Natalia Soledad Tissera, Berenice Freile, Romina Luca, Ivana Inés Pedraza, Federico Esteso, Diego Hernán Enrico, Federico Waisberg, Mariana Galli, Carolina Chacon, Fernando Sanchez Loria, Eduardo Huertas, Matias Rodrigo Chacon, Juan Manuel O'Connor
Journal: Journal of Clinical Oncology (2023)

146 Background: Short-course radiotherapy (SCRT) is an option in the neoadjuvant setting of resectable stage II-III rectal cancer, as well as in stage IV disease for local control without delay to initiate systemic treatment. Short-course radiotherapy is reported to be a comparable strategy for locally advanced rectal cancer. Limited data exist regarding the use of short-course radiation therapy when used as part of a non-surgical watch and wait approach. Methods: This is a retrospective analysis of all patients that underwent SCRT for rectal cancer at the Alexander Fleming Institute from 3/2014 to 6/2022. Results: 44 patients were treated with SCRT, 29 (66%) were male, with a median age of 59 years (46-73). Most of the patients had stage IV disease (26, 59,1%) followed by clinical stage II-III (18, 40,9%). 30 (68%) were localized in the middle with 14 (32%) in the lower rectum, by MRI imaging. In locally advanced disease 5/18 had T4 disease and 7/18 had N≥2. 14/18 patients (89%) underwent SCRT followed by consolidation chemotherapy (ChT) and 4 (11%) had induction ChT followed by SCRT. In metastatic disease 14/26 patients (53.84%) underwent SCRT followed by consolidation ChT, 10 (38.46%) had induction ChT followed by SCRT, and 2 (7.7%) received only SCRT. 29 (65.9%) of patients underwent surgery. 17/29(58.6%) had metastatic disease and 12/29 (41.4%) had locally advanced disease. Pathological response rates in operated patients were 2 (6.9%). 8 (18.2%) cases had a clinical complete response (cCR) (n=6 stage II-III and n=2 stage IV). Five (27.7% of the locally advanced group) patients with cCR underwent watch and wait with 1 local recurrence after 14 months. The remainder is disease free with a median follow-up time of 20 months (IC 95%: 15.14-24.85). Those that underwent SCRT following chemotherapy were more likely to have AEs compared to those that had chemotherapy following SCRT (11/30, 36.7% vs 25%, p=0.02). Conclusions: Our work shows that in a subgroup of patients diagnosed with LARC treated with SCRT followed by Chemotherapy, surgical treatment could be deferred after achieving a complete clinical response. The shorter time involved by SCRT allowed for less treatments with similar toxicity to long-course treatment regimens. SCRT is a reasonable option for local disease control in stage IV disease.
Optimal interval of surveillance gastroscopy after endoscopic resection for gastric neoplasia: A multicenter cohort study.
Authors: Byung-Wook Kim, Younghee Choe, Tae Ho Kim, Jun-Won Chung, Joon Sung Kim
Journal: Journal of Clinical Oncology (2023)

316 Background: Due to the possibility of metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection (ER) for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia (MGN). Methods: Medical records were reviewed retrospectively in patients who underwent ER for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into 2 groups; annual surveillance vs. biannual surveillance. The incidence of MGN was identified, and the risk factors for MGN were investigated. Results: Among the 1,533 patients, 677 patients were included (annual surveillance 302, biannual surveillance 375). The median follow-up for all patients was 22 (range, 12‒91) months. MGN was observed in 61 patients and metachronous gastric cancer (MGC) in 26 patients, both of which were not significantly different between the annual and biannual surveillance groups (annual vs. biannual: 26/302 vs. 32/273, P=0.989 in MGN; 13/302 vs. 13/373, P=0.582 in MGC). All the lesions were removed by ER successfully. In a multivariate analysis, severe atrophic gastritis on endoscopy was an independent risk factor for MGC (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P=0.008). H. pylori infection was not a significant risk factor in this study. Conclusions: Meticulous observation is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after ER for gastric neoplasia. Annual surveillance gastroscopy might be enough after ER for gastric neoplasia.
The impact of peri-operative chemotherapy on the outcomes of patients with non-metastatic cholangiocarcinoma.
Authors: Firas Baidoun, Muhamad Alhaj Moustafa, Omar Abdel-Rahman
Journal: Journal of Clinical Oncology (2023)

563 Background: Cholangiocarcinoma is a rare malignancy with poor prognosis and outcome despite therapy. It accounts for 2.2% of all new cancer cases and 5% of all cancer deaths. Surgical resection is still the main therapeutic approach, whereas the role of peri-operative chemotherapy is debatable. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with non-metastatic biliary adenocarcinoma at age 18 or older between 2004 and 2019. After excluding patients with unknown timing of surgery and chemotherapy, patients who died within 90 days of the most definitive primary site surgery and patients lost to follow-up, we split the cohort into three groups according to the clinical stage (stage I-III). Then, we evaluated the overall survival (OS) between the different treatment modalities (surgery only, adjuvant chemotherapy and neoadjuvant chemotherapy) in each group. We studied the OS using Kaplan-Meier estimates and multivariate cox regression analyses to evaluate factors associated with OS. Results: A total of 35,260 patients with non-metastatic cholangiocarcinoma were included in the analysis, of which 50.4% were females, 83% Caucasians, 9.5% African Americans. The median age at diagnosis was 70 (range 18-90). 14,757 (41.9%) were stage I, 12,472 (35.4%) stage II and 8,031 (22.8%) stage III. 7,286 (20.7%) had surgical resection only, 8,144 (23.1%) had chemotherapy only, 6,964 (19.7%) had surgical resection with perioperative chemotherapy and 12,866 (36.5%) did not receive any treatment. We compared survival between different treatment modalities based on clinical stage. In stage I, we found patient who were treated with surgery only had better median OS (mOS) compared to adjuvant chemotherapy (65.7 vs 50.4 months, P&lt;0.001) and no statistically significant difference between neoadjuvant chemotherapy and surgery only (mOS 79.8 vs 65.7 months, P=0.63). Whereas in stage II, patients who were treated with adjuvant and neoadjuvant chemotherapy had better mOS compared to those treated with surgery only (33.9 and 40.3 vs 29.9 months with P&lt;0.001 and P=0.005, respectively). Same trend was seen in stage III, patients who were treated with adjuvant and neoadjuvant chemotherapy had better mOS compared to surgery only (22.6 and 41.5 vs 19.5 months, respectively with P&lt;0.001 for all). In multivariate analysis, adjuvant and neoadjuvant chemotherapy did not affect the OS in all stages, except in stage III where neoadjuvant chemotherapy was associated with better OS (HR 0.646 95% CI 0.530-0.786; P&lt;0.001). Conclusions: Adjuvant and neoadjuvant chemotherapy do not seem to have survival benefit in early stage (stage I and II) cholangiocarcinoma. Whereas neoadjuvant chemotherapy tends to improve OS in stage III.
One-week versus two-week chemoradiotherapy followed by curative surgery in rectal cancer: Long-term comparative pooled analysis of two prospective multicenter phase II trials.
Authors: Jong Hoon Lee, Soo-Yoon Sung, Sung Hwan Kim
Journal: Journal of Clinical Oncology (2023)

96 Background: The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of one- and two-week chemoradiotherapy (CRT), respectively. We compare and report long-term outcomes by pooling data from two prospective trials for one- and two-week schedules of preoperative CRT and curative surgery in rectal cancer. Methods: Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during one week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions during two weeks with oral capecitabine. Results: A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival (OS) rate was 86.5% in one-week CRT and 85.3% in two-week CRT ( P = 0.84). The 5-year recurrence-free survival (RFS) rate was 83.5% in one-week CRT and 77.1% in two-week CRT ( P = 0.45). One patient (1.4%) in one-week CRT and eleven patients (13.8%) in two-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy ( P = 0.01). Downstaging (ypT0-2N0M0) occurred in 20 patients (28.2%) in one-week CRT and 27 patients (33.8%) in two-week CRT ( P = 0.50 ). One-week CRT arm had significantly higher acute hematologic (12.8% vs. 3.8%, P = 0.040) and non-hematologic (38.6% vs. 16.3%, P = 0.002) toxicities than two-week CRT arm. Conclusions: Both one- and two-week schedules of CRT showed favorable survival outcomes after seven years of follow-up. But, two-week course achieved more increased tumor response and decreased acute toxicity rather than one-week course. Clinical trial information: KROG 10-01 is registered at ClinicalTrials.gov (number, NCT01129700 ) and KROG 11-02 is registered at ClinicalTrials.gov (number, NCT01431599 ).
Internet-based assessment tools for predicting colorectal cancer risk: How do they communicate individualized risk to the young adult?
Authors: Allison Janak, Oliver Peacock, Michael White, Montserrat Guraieb-Trueba, Sa Thi Nguyen, Jumanah Alshenaifi, Scott Kopetz, Benny Johnson, Grace L. Smith, George J. Chang, Y. Nancy You
Journal: Journal of Clinical Oncology (2023)

72 Background: Online prediction tools for cancer risk can inform individuals about their risk and potentially encourage adoption of risk-modifying health behavior. The Colorectal Cancer Risk Assessment Tool (CCRAT) is an interactive tool developed by the National Cancer Institute for estimating colorectal cancer (CRC) risk for individuals between the ages of 45 and 85 without high risk predisposing conditions. Given the rising incidence of CRC among young adults under age 50, we aimed to investigate the performance of CCRAT in estimating their CRC risk. Methods: An institutional protocol prospectively enrolled 563 patients newly diagnosed with non-hereditary CRC and administered a health behavior questionnaire at baseline. Self-reported demographics, diet and physical activity, medication use, and family history were extracted and entered into the CCRAT ( https://ccrisktool.cancer.gov/calculator.html ) to calculate their predicted 5-year and lifetime CRC risks. Health behaviors and the predicted CRC risks in reference to the population average were compared among three groups: youngest- (aged 18-44, N = 276, 49%), young- (aged 45-50, N = 178, 32%), and older-onset (aged &gt; 50, N = 109; 19%). Results: The patient groups did not significantly differ in gender or in family history of CRC, but the youngest group had significantly more non-White patients (27, 22, vs. 19%; p = 0.008) and distal tumors (80, 76 and 65%; p = 0.05). The youngest and young groups had a higher prevalence of morbid obesity (18 and 15% vs. 12%; p = 0.002) and active smokers (6 and 8% vs. 3%; p = 0.005). There were no significant differences in vegetable intake, moderate exercise, NSAID use, or female hormone use. The 5-year CRC risk was correctly predicted as “higher than average population” for a significantly smaller proportion of the youngest (42%) and young (45%) patients, when compared to their older counterpart (71%; p &lt; 0.001). Similarly, the tool communicated “higher than average” lifetime risk for CRC in only 56 and 60% of the youngest and young patients, but 72% of the older ones (p = 0.021). Conclusions: The existing risk prediction tool inadequately communicated CRC risk for adults younger than 50 years of age. Risk factors underlying young-onset CRC likely differ from and extend beyond those as currently assessed. New tools capturing age-specific risk factors are needed to accurately communicate individualized risk and potentially motivate risk-modifying lifestyles.